{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:34:52Z","timestamp":1791484492585,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100548"],"award-info":[{"award-number":["82100548"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2022NSCQ\u2010MSX0094"],"award-info":[{"award-number":["CSTB2022NSCQ\u2010MSX0094"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Approximately 50% of the patients with ulcerative colitis (UC) are primarily nonresponsive to anti\u2010tumor necrosis factor (TNF) therapy or lose their responsiveness over time. The gut microbiota plays an important role in the resistance of UC to anti\u2010TNF therapy; however, the underlying mechanism remains unknown. Here, it is found that the transplantation of gut fecal microbiota from patients with UC alters the diversity of the gut microbiota in dextran sulfate sodium\u2010induced colitis mice and may affect the therapeutic responsiveness of mice to infliximab. Furthermore, the abundances of <jats:italic>Romboutsia<\/jats:italic> and <jats:italic>Fusobacterium<\/jats:italic> increase in the tissues of patients with UC who do not respond to anti\u2010TNF therapy. Differentially abundant metabolites are mainly enriched in nicotinate and nicotinamide metabolism in NCM460 cells after <jats:italic>Fusobacterium nucleatum<\/jats:italic> infection. Mechanistically, <jats:italic>F. nucleatum<\/jats:italic> promotes the nicotinamide adenine dinucleotide (NAD<jats:sup>+<\/jats:sup>) salvage pathway by upregulating NAMPT expression, which subsequently leads to the activation of the p38 mitogen\u2010activated protein kinase (MAPK) signaling pathway and promotes the secretion of inflammatory factors, ultimately inhibiting the therapeutic response to anti\u2010TNF drugs. These findings demonstrate that the gut microbiota can influence the response to anti\u2010TNF therapy in patients with UC and highlight the therapeutic potential of targeting <jats:italic>F. nucleatum<\/jats:italic> and its associated pathways for preventing and treating drug resistance in UC.<\/jats:p>","DOI":"10.1002\/advs.202413128","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T05:51:22Z","timestamp":1735537882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Gut Microbiota Affects Anti\u2010TNF Responsiveness by Activating the NAD<sup>+<\/sup> Salvage Pathway in Ulcerative Colitis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4577-4662","authenticated-orcid":false,"given":"Jing","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Renmin Hospital of Wuhan University  Hubei 430060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology Chengdu Second People's Hospital  Sichuan 610011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"He","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2774-374X","authenticated-orcid":false,"given":"Yongyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0205-x"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa252"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00188-17"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.07.025"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.06.019"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izac182"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8030438"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5358"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.594806"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.104964"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01324"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01280-z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310705"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314241"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa039"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-020-01892-0"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.06.077"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.133249"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01051-y"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0287-4"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2023.04.007"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00966-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-39012-w"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1910742"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01112-z"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23136966"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103329"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.11.304"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3363"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq4006"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12040800"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.658087"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2024.127660"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2287073"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1865708"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjw051"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136860"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.07.009"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080890"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322780"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.317276"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.06.004"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v30.i14.2018"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15061494"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.12185"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1681972"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001146"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318264"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4307"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S409290"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/SMMD.20230019"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016357.2010.492235"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21121752"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127378"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.09.028"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-007-9083-2"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202413128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T09:14:46Z","timestamp":1759742086000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202413128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":56,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/advs.202413128"],"URL":"https:\/\/doi.org\/10.1002\/advs.202413128","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,30]]},"assertion":[{"value":"2024-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2413128"}}